Biomolecular Engineering, Bioengineering, Biochemicals, Biofuels, and Food

State and specific growth estimation in heterologous protein production by Pichia pastoris

  1. José M. Barrigón1,
  2. Ramon Ramon1,
  3. Isabel Rocha2,
  4. Francisco Valero1,
  5. Eugénio C. Ferreira2,
  6. José L. Montesinos1,*

Article first published online: 22 NOV 2011

DOI: 10.1002/aic.12810

Issue

AIChE Journal

AIChE Journal

Volume 58, Issue 10, pages 2966–2979, October 2012

Additional Information

How to Cite

Barrigón, J. M., Ramon, R., Rocha, I., Valero, F., Ferreira, E. C. and Montesinos, J. L. (2012), State and specific growth estimation in heterologous protein production by Pichia pastoris. AIChE J., 58: 2966–2979. doi: 10.1002/aic.12810

Author Information

  1. 1

    Dept. of Chemical Engineering, Escola d'Enginyeria, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain

  2. 2

    IBB—Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, Universidade do Minho, 4710-057 Braga, Portugal

*Dept. of Chemical Engineering, Escola d'Enginyeria, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain

Publication History

  1. Issue published online: 10 SEP 2012
  2. Article first published online: 22 NOV 2011
  3. Accepted manuscript online: 31 OCT 2011 10:35AM EST
  4. Manuscript Revised: 29 SEP 2011
  5. Manuscript Received: 12 NOV 2010

Funded by

  • Spanish programme of Chemical Processes Technologies. Grant Numbers: CTQ2007-60347, CTQ2010-15131
  • Science and Innovation Ministry. Grant Number: HP2007-0045
  • Reference Network in Biotechnology (XRB) from the DURSI (Generalitat de Catalunya). Grant Number: 2009-SGR-00281
  • “Luso-Spanish Integrated Actions”. Grant Number: Action 100/08

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Keywords:

  • state estimation;
  • observers;
  • recursive least squares;
  • heterologous protein production;
  • Pichia pastoris

Abstract

Estimation of biomass, substrate, and specific growth rate (μ) by two nonlinear observers (nonlinear observer-based estimator—NLOBE, asymptotic observer with second-order dynamics tuning—AO-SODE) and a linear estimator (recursive least squares with variable forgetting factor—RLS-VFF) is presented. Heterologous protein production in Pichia pastoris PAOX1 (Mut+) and PFLD1-based systems is closely related to μ and has been addressed due to its high relevance in modern biotechnology and bioprocess engineering. μ was estimated by online gas analyses or substrate measurements, biomass, and substrate considering yield coefficients and mass balances. In simulation studies, NLOBE showed high sensitivity to tuning and initialization variables. Validation experiments demonstrated AO-SODE performs better than the RLS-VFF for moderate to rapid changes of μ and model parameters being known. If low changes on μ are presented, for instance, in substrate regulation, RLS-VFF comes up as the best option, because of its reduced requirements. © 2011 American Institute of Chemical Engineers AIChE J, 58: 2966–2979, 2012

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